Daisy-chain gene drives for the alteration of local populations
Name
8275.full.pdf
Description
Published version
Size
1.83 MB
Format
Adobe PDF
Checksum (MD5)
4803c89f1f597233e32b763c1648b52e
Author(s)
Noble, Charleston
Min, John
Olejarz, Jason
Buchthal, Joanna
Chavez, Alejandro
Smidler, Andrea L.
DeBenedictis, Erika A.
Church, George M.
Nowak, Martin A.
Esvelt, Kevin Michael
Date Issued
April 2019
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Noble, Charleston et al. "Daisy-chain gene drives for the alteration of local populations." Proceedings of the National Academy of Sciences 116, 17 (April 2019): 8275-8282 © 2019 National Academy of Sciences
Version
Final published version
Abstract
If they are able to spread in wild populations, CRISPR-based gene-drive elements would provide new ways to address ecological problems by altering the traits of wild organisms, but the potential for uncontrolled spread tremendously complicates ethical development and use. Here, we detail a self-exhausting form of CRISPR-based drive system comprising genetic elements arranged in a daisy chain such that each drives the next. “Daisy-drive” systems can locally duplicate any effect achievable by using an equivalent self-propagating drive system, but their capacity to spread is limited by the successive loss of nondriving elements from one end of the chain. Releasing daisy-drive organisms constituting a small fraction of the local wild population can drive a useful genetic element nearly to local fixation for a wide range of fitness parameters without self-propagating spread. We additionally report numerous highly active guide RNA sequences sharing minimal homology that may enable evolutionarily stable daisy drive as well as self-propagating CRISPR-based gene drive. Especially when combined with threshold dependence, daisy drives could simplify decision-making and promote ethical use by enabling local communities to decide whether, when, and how to alter local ecosystems.
MIT Department
Massachusetts Institute of Technology. Media Laboratory
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1716358116
